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c‐Kit and c‐kit mutations in mastocytosis and other hematological diseases
Author(s) -
Boissan Mathieu,
Feger Frédéric,
Guillosson JeanJacques,
Arock Michel
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.67.2.135
Subject(s) - biology , systemic mastocytosis , proto oncogene proteins c kit , immunology , mutation , genetics , haematopoiesis , mast cell , stem cell factor , gene , stem cell
Mast cells (MC) are tissue elements derived from hematopoietic stem cells. Their differentiation and proliferation processes are under the influence of cytokines, including one of utmost importance known as stem cell factor (SCF). SCF receptor is encoded by the protooncogene c‐kit, belongs to the type III receptor tyrosine kinase subfamily, and is also expressed on other hematopoietic or non‐hematopoietic cells. Ligation of c‐kit receptor by SCF induces its dimerization, followed by induction of multiple intracellular signaling pathways leading to cell proliferation and activation. Mastocytosis, a relatively rare group of diseases characterized by accumulation of MC in various tissues, are found isolated or sometimes associated with other hematological malignancies in humans. Although the initial events leading to mastocytosis are not yet unraveled, alterations of the c‐kit gene have been described. Particularly interesting are acquired mutations resulting in a constitutively activated receptor, possibly involved in the increased numbers of MC in tissues. For this reason, future strategies might be envisaged to target specifically the mutated c‐kit and/or its intracellular signaling. J. Leukoc. Biol. 67: 135–148; 2000.